CME available

Congenital cytomegalovirus (cCMV) is the most common infectious cause of birth defects and the leading cause of non-genetic sensorineural hearing loss. Early diagnosis and treatment of infants helps improve outcomes. cCMV was recently added to the Los Angeles County Reportable Diseases and Conditions list. This article covers the background, clinical presentation, diagnosis, management, and reporting of cCMV, as well as the importance of surveillance and reporting.

Background

Congenital cytomegalovirus (cCMV) is the most common congenital viral infection as well as the most common cause of non-genetic sensorineural hearing loss in the United States and worldwide.¹ Additionally, cCMV can cause long-term neurodevelopmental disabilities including intellectual disability and visual impairment.

CMV is a double-stranded DNA virus that belongs to the Herpesviridae family (which includes herpes simplex virus types 1 and 2, varicella-zoster virus, and Epstein-Barr virus). These viruses have the ability to establish lifelong latency and may reactivate under certain conditions. Humans are the main reservoir.^2,3

Maternal CMV infection and fetal transmission risk

The risk of cCMV depends on the stage of maternal infection. Maternal CMV infection can be primary (a first-time infection) or non-primary (reactivation of an existing infection or reinfection with a different strain).⁴ The risk of transmission to the fetus and the severity of the congenital disease are higher with primary infection, especially in the first trimester.⁴ Fetal infection occurs in 1 out of 3 cases (33%) when the pregnant person has a primary infection. Unlike congenitally acquired CMV, CMV infection acquired postnatally in full term infants is usually asymptomatic and causes no long-term effects. Postnatal CMV acquired in premature infants can cause serious illness.

Routes of transmission

CMV is primarily shed in body fluids such as saliva, urine, breast milk, and blood. Pregnant people become infected most often through close contact with young children or through sexual transmission.⁵

Congenital CMV in Los Angeles County

According to the Centers for Disease Control and Prevention (CDC), 1 in 200 babies are born with cCMV infection.⁹ This suggests that up to 500 babies may be born with cCMV infection in LA County each year. According to the CDC, about 1 in 5 babies with cCMV infection will have birth defects or long-term health problems.⁹ Mandated reporting of cCMV by laboratories and providers will provide a more accurate picture of cCMV burden and impact in LA County.

Which Infants Should Be Tested for cCMV

Testing for cCMV should be performed in newborns (within the first three weeks of life) if they:

• Have clinical signs or findings suggestive of cCMV, including:
  • Conjugated hyperbilirubinemia or elevated liver function tests
  • Hepatosplenomegaly
  • Thrombocytopenia or petechial rash
  • Microcephaly (head circumference less than 10th percentile)
  • Small for gestational age (birth weight less than 10th percentile)
• Have evidence of intrauterine growth restriction or abnormalities on fetal US (ascites, intracranial calcifications, or echogenic bowel)
• Did not pass the newborn hearing screen (one or both ears)
• Were born to a mother with HIV¹⁰
• Were born to a mother who tested positive for CMV during pregnancy

Diagnosis

Timing of testing is an important consideration for distinguishing cCMV from postnatally acquired CMV. At all ages, polymerase chain reaction (PCR) is the standard diagnostic test for cCMV. cCMV infection cannot be diagnosed with antibody testing (IgG, IgM).

Dried blood spot testing

Dried blood spots (DBS) collected at birth for newborn screening can be used to diagnose cCMV. These samples can be requested from the California Newborn Screening Program and sent to a commercial laboratory for CMV DNA detection by PCR.¹²

To request DBS, your facility/laboratory should contact the California Newborn Screening Program at CaliforniaBiobankCMV@cdph.ca.gov.

Management

Once a diagnosis of cCMV is made, providers should initiate the following evaluations and referrals:⁸

• Laboratory testing: Complete blood count and liver function tests including direct bilirubin level.
• Neuroimaging: Head ultrasound or MRI.
• Audiologic evaluation: Initial hearing assessment, with subsequent frequent follow-up throughout early childhood to monitor for delayed-onset hearing loss.
• Ophthalmologic assessment at birth and periodically throughout early childhood.
• Referral to a California Department of Developmental Services Regional Center for early intervention services.
• Consultation with an infectious disease specialist to assess the potential benefits of antiviral therapy and weigh them against the side-effect profile.

Antiviral Treatment

• Oral valganciclovir or intravenous ganciclovir are first-line antiviral agents for treatment for cCMV. Treatment is recommended for infants with symptomatic cCMV, with studies showing benefit if initiated within the first month of life.¹³
• Expert opinion varies regarding benefit of antiviral therapy in infants with isolated hearing loss.
• Antiviral therapy is not recommended for asymptomatic cCMV.

Prevention

There are several vaccine candidates aiming to reduce the risk of cCMV in clinical trials, but a licensed vaccine is likely years away. Until then, the primary prevention strategy is for pregnant individuals and those planning to become pregnant to practice hygiene-related measures that reduce exposure to saliva and urine from babies and young children.^14,15 These include:

• Avoiding contact with saliva when kissing a child
• Not putting a pacifier in their mouth
• Not sharing food, utensils, drinks, or straws
• Not sharing toothbrushes
• Washing hands after changing diapers.

Image courtesy www.NationalCMV.org. Download education resources.

Reporting

Health care providers must report all cCMV diagnoses in Los Angeles County residents. Reports must be submitted to the Department of Public Health within 7 calendar days of diagnosis.

• Fax a CMR to 888-397-3778 or 213-482-5508; OR
• SEND via secure email to ACDC-MorbidityUnit@ph.lacounty.gov; OR
• CALL 888-397-3993 weekdays, 8:30 am–5:00 pm. For more information about reporting, visit the LA County Provider Communicable Disease Reporting webpage.

Conclusions

cCMV is the most common vertically transmitted infection and the leading cause of non-genetic sensorineural hearing loss. cCMV is now a reportable disease. Accurately assessing the disease burden will increase awareness among providers and the public and lead to increased prevention, treatment, and improved management of cCMV.

Resources

For providers:

• Congenital CMV | LA County
• CMV Factsheet for Healthcare Providers | CDC
• Clinical Overview of CMV and Congenital CMV for Healthcare Providers | CDC
• Cytomegalovirus and pregnancy | March of Dimes
• Congenital Cytomegalovirus | American Academy of Pediatrics
• Cytomegalovirus in Pregnancy FAQs | American College of Obstetricians and Gynecologists

For parents:

• National CMV Foundation
• CMV Factsheet for Pregnant Women and Parents | CDC
• What Parents Need to Know About CMV | American Academy of Pediatrics

References

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